Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication In Vitro and In Vivo

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  • WU Hong-Xia
    College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • WANG Hua-Lei
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • GUO Xiao-Feng
    College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China
  • YANG Yu-Jiao
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • MA Jin-Zhu
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • WANG Tie-Cheng
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • GAO Yu-Wei
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • ZHAO Yong-Kun
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • YANG Song-Tao
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
  • XIA Xian-Zhu
    Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China

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タイトル別名
  • Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication <i>In Vitro</i> and <i>In Vivo</i>

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To investigate the potential of adeno-associated viruses serotype 2 (AAV2)-mediated RNA interference (RNAi) as an antiviral agent against rabies, recombinant AAV2 vectors expressing siRNA targeting the nucleoprotein (N) gene of rabies virus (RABV) (rAAV-N796) were constructed and evaluated. When NA cells pretreated with rAAV-N796 were challenged with RABV, there was a 37.8 ± 3.4% to 55.1 ± 5.3% reduction in RABV virus titer. When cells pre-challenged with RABV were treated with rAAV-N796, there was a 4.4 ± 1.4 to 28.8 ± 3.2% reduction in RABV virus titer. Relative quantification of RABV transcripts using real-time PCR and Western blot revealed that the knockdown of RABV-N gene transcripts was based on the rAAV-N796 inoculation titer. When any NA cells were treated with rAAV-N796 before or after challenged with RABV, significant reduction in virus titer was observed in both administrations. Mice treated intracerebrally with rAAV-N796 exhibited 50 ± 5.3 and 62.5 ± 4.7% protection when challenged intracerebrally or intramuscally, respectively, with lethal RABV. When mice treated intramuscularly with rAAV-N796 were challenged intramuscularly with lethal RABV, they exhibited 37.5 ± 3.7% protection. When mice were intracerebrally and intramuscularly with rAAV-N796 24 hr after exposure to RABV infection, they exhibited 25 ± 4.1% protection The N gene mRNA levels in the brains of challenged mice with three different administrations were reduced (55, 68, 32 and 25%, respectively). These results indicated that AAV2 vector-mediated siRNA delivery in vitro in NA cells inhibited RABV multiplication, inhibited RABV multiplication in vivo in the mice brain and imparted partial protection against lethal rabies. So, it may have a potential to be used as an alternative antiviral approach against rabies.

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